Clara Barton established the American Red Cross in 1881 with the primary objective of providing emergency assistance and disaster relief to people in the United States. The organization later grew into one of the largest charitable and nonprofit organizations, expanding its reach into blood product supply, cellular therapies, and tissue services. Leaders had the foresight to incorporate histocompatibility and immunogenetics laboratory services in key regions within the United States, with the intent of providing compatibility services to hospitals in need of matched platelet units to support patients diagnosed with platelet refractoriness. The first histocompatibility laboratory was established in Dedham, Massachusetts, in the late 1970s. In 1980, additional laboratories were placed in Portland, Oregon; Charlotte, North Carolina; and Philadelphia, PA. These locations were critical in serving the transfusion needs of area hospitals with specialized programs in hematologic malignancies.
Human leukocyte antigens (HLA) are proteins that are expressed on the surface of most cells and are critical markers that determine compatibility between a donor and recipient. The crucial role of the HLA system in hematopoietic stem cell (HSC) transplantation as well as platelet transfusion naturally led to an additional offering of testing to support transplant programs. Between 2001 and 2016, the laboratory in Dedham expanded its services to include bone marrow transplant support, while the laboratory in Philadelphia managed the cord blood transplantation contract and the unrelated-donor registry from the National Marrow Donor Program (NMDP). HSCs come from related and unrelated donors as well as cord blood units. As we celebrate National Cord Blood Awareness Month, the involvement of the American Red Cross in supporting HSC transplantation is highlighted here.
Stem cells originate from the bone marrow and are a population of immature and undifferentiated cells that can become any number of cell types. Like blood transfusion, HSC transplantation involves the infusion of cells–in the latter case, stem cells in patients with blood disorders, immune system disorders and inherited metabolic disorders with the goal of generating new and functional cells. The most successful HSC transplantation is that in which the stem cell recipient and the donor share the same HLA molecules as this prevents an immune reaction against the infused stem cells of the donor or against the patient’s own tissues.
The laboratories use state-of-the-art sequencing technology to determine the HLA genotypes of transplant candidates and their potential donors. The assays require isolation of DNA from patient and donor cells in blood, buccal swabs, or tissue and meticulous specimen preparation for sequencing using multiple next generation sequencing platforms. Histocompatibility technologists undergo rigorous training prior to performing bench work. Once HLA typing data is obtained, highly specialized laboratory personnel compile data and provide a comprehensive report on the degree of matching between donor and recipient based on analysis of the most relevant HLA antigens. Given that sensitization against HLA antigens also creates a barrier for successful transplantation, detection of antibodies that may be directed against the cells of a donor is another important tool in the transplant evaluation. HLA antibodies are detected in the serum of transplant candidates using microparticle bead assays, run on a Luminex platform. Finally, donor cells and patient serum are used in a crossmatch assay to confirm that components in the patient serum will not bind and destroy donor cells in vivo. The results of the HLA typing, HLA antibody and crossmatch tests are evaluated together and discussed with clinicians. This testing algorithm follows the guideline set by the National Marrow Donor Program as well as the American Society for Histocompatibility and Immunogenetics, accrediting agency for the Red Cross laboratories. For an overview of criteria for donor selection, we recommend a review by Timofeeva et al (1).
The estimated global incidence of the blood cancers leukemia, lymphoma, and myeloma is 1.28 million per year (2). The services provided by the American Red Cross laboratories are significant in assisting with lifesaving transplantation for patients with these cancers. These services are also in line with another current initiative of the American Red Cross, launched in 2021, to reach more blood donors to help patients with sickle cell disease. HSC transplantation is considered a curative treatment for this disease. Although not yet used broadly for this purpose, the tools and expertise that will further assist in research on this treatment and its clinical application are available under the same umbrella.
Contributors:
The history of the HLA labs was recounted by Drs. Neng Yu, Susan Hsu and Zahra Kashi, first directors of these laboratories.
References:
1. Timofeeva OA, Philogene MC, Zhang QJ. Current donor selection strategies for allogeneic hematopoietic cell transplantation. Hum Immunol. 2022 Oct;83(10):674-686.
2. Global Cancer Observatory [Internet]. Lyon, France: International Agency for Research on Cancer; c1965-2023. World; 2021 Mar [cited 2023 Jun 7]; [2 p.]. Available from: https://gco.iarc.fr/today/data/factsheets/populations/900-world-fact-sheets.pdf.
